Project Summary/Abstract An alarming number of adolescents will engage in substance use (including alcohol, tobacco, marijuana and opioids) before they leave high school, a fact that has serious long-term health and societal impacts. Since most adolescents begin using substances with peers, an understanding of the processes that lead to peer influence susceptibility in the context of substance-using peers offers critical avenues for successful intervention in substance use. Our prior research developed a unique performance-based experimental paradigm for measuring peer influence susceptibility and found that individual differences in susceptibility interact with adolescents? perceptions of their peers? substance use to predict their own substance use engagement. However, it remains unclear why some adolescents are more susceptible to peer influence than others, and how development confers increased risk for susceptibility. This work will examine the neural correlates associated with individual differences in peer influence susceptibility. Specifically, we will assess how increased functional connectivity within and between neural networks subserving greater sensitivity to social rewards and punishments, motivation to attain rewards and avoid punishment, and representations of social others is associated with greater peer influence susceptibility. We will also examine a network involved in executive control as a protective factor against later substance use. Using a two-cohort, accelerated longitudinal design including adolescents spanning grades 6-12, we will investigate how individual differences in connectivity within and between candidate neural networks predict prospective substance use initiation in the context of peers. Eight hundred adolescents (age 11-13 years) will complete baseline assessments of substance use, and peer influence susceptibility using an innovative experimental paradigm. A subset (n = 250) of the initial sample will partake in longitudinal task-based functional imaging in year 1 and 3, as well as multi-wave longitudinal assessment occurring at one-year longitudinal intervals in subsequent years 2-5 to obtain extensive data on adolescents? and peers? substance use trajectories across a critical developmental period associated with substance use. By delineating the neurobiological markers of social influence susceptibility, project findings can characterize those individuals at greatest risk for substance use, which can inform interventions by targeting the psychological processes that contribute to peer influence susceptibility.